Immune responses to cell surface entigens such as major histocompatibility complex (MHC) and tumor specific antigens are T-cell dependent and involve the collaboration of different lymphoid cell subpopulations. The precise nature of this collaboration and the genetically determined pathways giving rise to antigen specific effector cells are problems that we propose to approach. Antigenic stimulus can result in the differentiation of distinct cell subpopulations with different functions in the mediation of immune responses; cytolytic T-cells, suppressor T-cells, lymphokine producing B-cells and antibody producing B-cells. In most cses the maturation of each of these responses is dependent upon regulatory T-cells. There may be further subdivisions within this regulatory or helper T-cell population depending upon which functional subset of pre-effector cells they will aid. The mechanisms of cell-cell interactions and the interrelationship of helper functions for T- and B- effector cell responses can be approached by the development of systems in which each subpopulation's contribution to the response can be studied independently. Our approach is to study the requirements for helper cell development and the production of soluble regulatory products in one system and the role that these products served in the generation of effector cells in another. Since soluble factors can replace functions of helper T-cells mediating antibody production and killer cell differentiate the relationship of helpers to each response can be approached. Also, we will take advantage of genetic and artificially induced situations (ALS suppressed mice) in which low or minimal responses to antigens of syngeneic tumors and the MHC are observed. We will investigate the ability of these animals to product regulatory factors or to "accept" exogenous sources of helper substances such that high responses might be attained.